Structural, functional and regulatory aspects of membrane-bound monamine oxidases will be studied using a combination of biophysical and biochemical methods. Size, geometry and local polarity characterizing the active site and its integration into the membrane matrix, as well as proximity between the sites, will be measured directly with a series of active-site directing spin-labeled pargyline with varying chain lengths. The nature of the specific lipid-protein interactions localized at the vicinity of the active site region, which are crucial to the functional differentiation of MAO-A and MAO-B enzymes, will be studied. Dynamic interconversion, the hypothetical regulatory mechanism of the MAO-membrane system, may be investigated by monitoring the change in ESR signal originated from spin probes covalently linked to the active center under appropriate conditions. Methodologies established will be applied to obtain knowledge of postmaturational age-related changes in these parameters in regional parts of the brain. The information will be useful in understanding the relationship of brain MAO to the molecular mechanism of cellular aging occurring in the monoaminergic system.